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Purpose: Discovery of effective, orally acting, small molecular weight inhibitors of TNF-a production for the treatment of RA and other diseases in which TNF-a plays important role in pathogenesis. Methods: Synthesis of new dibenzo[e, h]azulenes and their testing in several inflammatory models (LPS induced TNF-a production, LPS induced shock, writhing and hot plate models of analgesia, carrageenan induced paw edema and adjuvant induced arthritis model). Results: Members of different classes of dibenzo[e, h]azulenes inhibit TNF-a production in vitro in low micromolar range. Selected compounds administered per-orally showed potent inhibition of LPS induced TNF-a secretion in vivo. They also exhibit excellent activity in different acute inflammatory models such as LPS induced shock and carrageenan induced paw edema. Activity of some dibenzo[e, h]azulene compounds was confirmed in adjuvant induced arthritis model in rats when they had been dosed perorally in established phase of the disease. Effects included not only decrease in degree of inflammation but also remarkable attenuation of degenerative processes reversing histopathological changes that are characteristic for RA. In addition, these compounds have analgesic activity comparable to that of acetylsalicylic acid when tested in the writhing model of analgesia. Conclusions: Good toxicology profile, lack of genotoxicity and good safety profile indicate that dibenzo[e, h]azulene class of orally available TNF-a inhibitors could bring disease modifying activity and symptomatic relief to RA patients.

Amorphous precursors of HfO2-AlO1.5 and ZrO2-AlO1.5 systems covering the whole concentration range were co-precipitated from aqueous solutions of the corresponding salts. The thermal behaviour of the amorphous precursors was examined by differential thermal analysis, X-ray powder diffraction (XRD), laser Raman spectroscopy and scanning electron microscopy. The crystallization temperature of both systems increased with increase in the AlO1.5 content, from 530 to 940degreesC in the HfO2-AlO1.5 system, and from 405 to 915degreesC in the ZrO2-AlO1.5 system. The results of phase analysis indicate an extended capability for the incorporation of Al3+ ions in the metastable HfO2- and ZrO2-type solid solutions obtained after crystallization of amorphous co-gels. Precise determination of lattice parameters, performed using whole-powder-pattern decomposition method, showed that the axial ratio c(1)/a(f) in the ZrO2- and HfO2-type solid solutions with 10mol% or more of Al3+ approach 1. The tetragonal symmetry of these samples, as determined by laser Raman spectroscopy, was attributed to the displacement of the oxygen sublattice from the ideal fluorite positions. It was found that the lattice parameters of the ZrO2-type solid solutions decreased with increasing Al3+ content up to similar to10 mol%, whereas above 10 mol%, further increase of the Al3+ content has very small influence on the unit-cell volume of both HfO2- and ZrO2-type solid solutions. The reason for such behaviour was discussed. The solubility of Hf-4+ and Zr4+ ions in the aluminium oxides lattice appeared to be negligible.

Dibenzo[b, f]oxepines and dibenzo[b, f]thiepines were recognized as useful starting compounds for the synthesis of various dibenzo[e, h]azulenes which numerous derivatives show different pharmacological activities [1, 2]. Herein we wish to report some efficient syntheses of a few tetracyclic dibenzo[e, h]azulenes starting from 11H-dibenzo[b, f]oxepin-10-one and its sulphur analogue (1). Common synthetic strategy for the synthesis of different dibenzo[e, h]azulene scaffolds comprises formation of a-substituted ketones (by reaction of activated methylene group of ketones 1 with various reagents), which are further transformed into appropriate tetracyclic dibenzo[e, h]azulene system via nucleophilic substitution and elimination reaction mechanisms. According to target molecules requested, those tetracyclic compounds can be further transformed by different functional group interconversions.

The amorphous precursors of the ZrO2-GaO1.5 system at the ZrO2-rich side of the concentration range were prepared by the co-precipitation from aqueous solutions of the corresponding salts. Thermal behaviour of the amorphous precursors was monitored using differential thermal analysis, X-ray powder diffraction (XRD) and Raman spectroscopy. The crystallization temperature of the amorphous precursors increased with an increase in the GaO1.5 content, from 435 °C (0 mol % of GaO1.5) to 720 °C (50 mol % of GaO1.5). The results of phase analysis indicated an extended capability for the incorporation of Ga3+ ions in the metastable ZrO2-type solid solution obtained after crystallization of amorphous co-gels. However, solubility significantly decreased with further temperature treatment. The results of XRD and Raman spectroscopy showed that the incorporation of Ga3+ ions partially stabilized only tetragonal polymorph of ZrO2. Precise determination of lattice parameters, performed using whole-powder-pattern decomposition method, showed that the unit-cell volume of t-ZrO2 type solid solutions decreases linearly with the increase of Ga3+ content. The obtained results were compared with the results obtained for some other trivalent undersized dopant cations (Al3+, Cr3+, and Fe3+).

The tricyclic structure of dibenzo[b, f]oxepines and dibenzo[b, f]thiepines was identified as an interesting scaffold which numerous derivatives show different pharmacological activities (antipsychotic, sedative, antidepressant, analgesic, antihypertensive, nonsteroidal anti-inflammatory, tromboxane antagonism). This broad biological activity prompted use of dibenzo[b, f]oxepines and dibenzo[b, f]thiepines as intermediates for the synthesis of various polycyclic compounds. Herein we wish to report some efficient syntheses of a few tetracyclic dibenzo[e, h]azulenes starting from 11H-dibenzo[b, f]oxepin-10-one and its sulphur analogue (1). According to target molecules requested, those tetracyclic compounds can be further transformed by different functional group interconversions.

The X-ray crystal structure analysis of the title compound revealed chair conformation of the pyranosyl ring. The structure shows no deviations from the geometric parameters of pyranoside carbohydrates.

A series of iron/titanium oxide nanocrystalline particles with the Fe/Ti molar ratio up to 0.15 was synthesized by the modified sol-gel procedure. Ti(IV)-isopropoxide and anhydrous Fe(II)-acetate were used as precursors of titanium and iron. The precursors were mixed and subsequently hydrolyzed with water molecules generated “in situ” by an esterification reaction between acetic acid and ethanol. FT-IR spectra showed that acetate groups were chemically bound to the metal cation. The Raman spectra of as-synthesized samples exhibited relative strong and sharp band at 2937 cm-1 associated with bands at 3022 and 2985 cm-1, as a result of stretching vibrations of CH2 and CH3 groups of unhydrolyzed organic precursor. Thermogravimetric analysis (TGA) showed that the weight loss was accelerated and completed at a lower temperature as the relative concentration of iron in Fe-TiO2 samples increased. Thermal analysis proved the evaporation of solvents and thermal degradation of loosely bound organic molecules at a temperature up to 260oC. The strong exothermic peak in DTA curve between 300-450oC was due to the amorphous-anatase transition related to the thermal degradation of strongly bound organic molecules, condensation of unhydrolyzed –OR groups, sintering and growth of particles and a rearrangement of newly formed chemical bonds. With the addition of iron this exothermic peak shifted to lower temperatures, became more asymmetric and was completed in a narrower temperature range. As-synthesized samples were amorphous for XRD independently of the relative amount of doped iron. The undoped samples and samples doped with 1 mol% of iron, thermally treated up to 500oC, contained anatase as the dominant phase and rutile as the minor phase. The samples having 15 mol% of iron, thermally treated at the same temperature, contained anatase (major phase), rutile (minor phase) and a very small amount of an unidentified phase. The crystallite size of the dominant phase in samples was estimated from the XRD line broadening using the Scherrer formula. Scanning electron micrographs of undoped samples heated at 500oC showed large irregular aggregates of nanocrystalline TiO2 particles with a relatively flat surface. On the contrary, the samples doped with 5 and 15 mol% of iron and treated at the same temperature exhibited a non-uniform sponge-like surface with rather uniformly distributed micrometer holes. Also, much smaller aggregates growing up from the surface of big ones were visible. The present result showed a remarkable influence of iron on the morphology of iron-doped TiO2 samples. In addition, XRD results differed from many similar investigations that considered only the presence of hematite or pseudobrookite as segregated iron phases in iron-doped TiO2 powder samples.

Pyridine adducts of Co, Ni, Cu and Zn sulfate were obtained by refluxing the corresponding sulfate with pyridine in chloroform. The compounds were characterized by elemental analysis, x-ray powder diffraction and FTIR spectroscopy. The elemental and thermal analysis results revealed that the formulae of the complexes are M2(SO4)2xC5H5NyH2O where x=2, 3, 2, and 1 and y=6, 4, 6 and 4 for the Co, Ni, Cu and Zn compound, respectively. The complexes were not found to be isostructural, but certain structural similarities were observed between Zn and Co compounds. Although the thermal decomposition pathways of the various compounds were quite different and each consisted of several steps, in all cases the dehydration preceded the depyridination. The spectral data are discussed with regard to the thermal behaviour. Appreciably strong hydrogen bonding and pronounced structural differences relating the sulfate ions were presumed for the Cu compound.

In continuation of our research on the materials with improved catalytic efficiency we investigated the systems ZrO2-Fe2O3 and HfO2-Fe2O3 having Fe2O3 content up to 50 mol %. Amorphous precursors of ZrO2-Fe2O3 and HfO2-Fe2O3 systems were co-precipitated from aqueous solutions of the corresponding salts. Detailed studies of the crystallization behavior of the precursors were performed by differential thermal analysis and thermogravimetric analysis. Crystallization temperature of both systems increased with an increase of the Fe2O3 content indicating that in both cases the amorphous precursor was a single co-gel. The influence of temperature treatment (500, 600, 800 and 1100 °C) on the phase development in the ZrO2-Fe2O3 and HfO2-Fe2O3 systems was studied by X-ray powder diffraction (XRD) and, in some cases, by laser Raman spectroscopy. XRD patterns were taken by step-scanning and determination of unit-cell parameters of the appropriate phases was performed by means of the powder-pattern-fitting methods. It was found that incorporation of Fe3+ ions partially stabilizes high temperature polymorphs of zirconia and hafnia during the calcination and cooling at standard air pressure. Incorporation of Fe3+ ions into ZrO2 and HfO2 lattices decreases with the increase of temperature, which was followed by the transformation of metastable polymorphs to the thermodynamically stable monoclinic polymorphs of zirconia and hafnia. The terminal solid solubility limits of Fe2O3 in ZrO2, estimated at RT, was ~30 mole % for calcination at 600 °C, ~9 mole % for calcination at 800 °C and  2.0 mole % for calcination at 1100 °C. The terminal solid solubility limits of Fe2O3 in HfO2, estimated at RT after the same calcination procedures, showed to be very similar, only ~1 mole % smaller. In both systems the unit cell volume of the crystallization products decreased with the increase of iron content, but in the system ZrO2-Fe2O3 the rate of decrease was bigger. The status of the Fe3+ ions in the HfO2- and ZrO2-type lattice and the process of their segregation into the  -Fe2O3 phase were examined by Mössbauer spectroscopy.

Spectroscopic (IR, UV/VIS) and thermal (TG, DTA) studies of the monoethyl (HL1) and monobutyl (HL2) esters of [alpha-(4-benzeneazoanilino)-N-benzyl]phosphonic acid and their cyclopalladated binuclear complexes, [PdLCl]2, as well as mononuclear chelate complexes, PdL_2, have been carried out to determine structural and decomposition properties of these biologically interesting compounds. Thermal decomposition of the complexes takes place through a multistep process. In the chloro-bridged cyclopalladated complexes ligand deesterification coupled with dehalogenation is followed by complex pyrolysis, while decomposition of the mononuclear complexes includes deesterification and other ligand degradation processes that leads to metallic palladium and P_2O_5. The X-ray and infrared spectroscopic study confirmed this mixture as the final residue in both types of complexes. No stable intermediate products were found during the thermal decomposition due to its complexity and to the overlap of the degradation processes. The spectral and thermal properties of the complexes were compared with those obtained for the complexes of dialkyl [alpha-(4-benzeneazoanilino)-N-benzyl]phosphonates and discussed with respect to their structure-stability relationship.

Sintetizirane su serije aciliranih derivata metil a-D-manopiranozida i metil-b-D-galaktopiranozida. Neki su derivati iz manozne serije podvrgnuti enzimskoj hidrolizi kataliziranoj esterazama iz seruma kunića i zamorca.

Thermal study (TG, DTA) of the palladium(II) complexes of monoethyl 2-quinolymethylphosphonate (2-mqmp): neutral dihalide adducts Pd(2-mqmp)_2X_2, ion-pair salt complexes [2-Hmqmp] ^+ [Pd(2-mqmp)X_3] ^- (X=Cl, Br) and chelate dihydrate Pd(2-mqmp-H)_2 2H_2O, has been carried out in order to determine decomposition properties of these biologically interesting complex compounds. Thermal decomposition of the complexes occurs in two steps: dehalogenation along with ligand deesterification is followed by complex pyrolysis that leads to the residue identified as a mixture of the metallic Pd and P_2O_2, what was confirmed by the infrared spectroscopic study. No stable intermediate products, except the corresponding anhydrous complex in the case of chelate compound, were found during the thermal decomposition due to the complexity and the overlap of the degradation processes. The results obtained were compared with those obtained for the complexes of diethyl 2-quinolylmethylphosphonate and discussed with respect to their cytostatic activity

On evaporation at room temperature of an aqueous mixture of Ln(III) sulphate and ethanol ammonium sulphate in a molar ratio higher than 1:12, in the presence of sulphuric acid, double sulphates of Sm, Eu, Ho, Tm, Yb and Y with a waxy feel were obtained. The stoichiometry of the obtained compounds was determined by means of elemental and TG analysis. On the basis of x-ray powder diffraction patterns it was concluded that an isostructural group with a general formula Ln2(HOCH2CH2NH3)8(SO4)7.8H2O was obtained. The above compounds have a stoichiometry and a crystal structure different from those of the double sulphates of La, Ce, Pr and Nd with the same monovalent cation, as presented earlier. The thermal decomposition of the investigated compounds in the temperature range from ambient temperature up to 1173 K occured in a similar way, mainly in three not well-differentiated steps. Lanthanide oxysulphates were obtained as final product.

The crystallisation of xFe/sub 2/O/sub 3/(100-x)P/sub 2/O/sub 5/, (14

Heksanuklearni etanolatni klusteri [M_6X_(12)(C_2H_5OH)_6]X_2, M = Nb, Ta; X = Cl, Br, sa slabo vezanim molekulama etanola, pokazali su se kao vrlo pogodni polazni spojevi u reakcijama niobijevih i tantalovih M_6-klustera s ligandima koji imaju dušikove atome kao donore. Otapanjem polaznih etanolatnih klustera [M_6X_(12)(C_2H_5OH)_6]X_2 u N,N-dimetilformamidu, uz tehniku rada na visokom vakuumu, priređeni su kristalni spojevi sastava [M_6X_(12)(C_3H_7ON)_6]X_2, M = Nb, Ta; X = Cl, Br, u kojima su svi terminalni oktaedarski položaji u klusterskoj jedinki zauzeti kisikom iz N,N-dimetilformamida. Reakcijom polaznih etanolatnih klustera i 1,5-naftiridina u etanolu dobiveni su spojevi u kojima, u danim uvjetima, nije došlo do potpune izmjene molekula etanola molekulama 1,5-naftiridina, [M_6Cl_(12)(1,5-C_8H_6N_2)_(4/2)(C_2H_5OH)_2]Cl_2. Novi su spojevi opisani na temelju elementarnih analiza, spektroskopskih i magnetskih mjerenja te kristalografskih podataka.

Nanosized titanium dioxide powders were prepared using sol-gel procedure. The selected colloidal suspensions were stabilized with polyethylene glycol. This polymer prevented sintering of TiO_2 particles during the calcination of the starting material. X-ray powder diffraction showed that the samples, obtained up to 773 K , were a mixture of anatase and brookite. In the samples obtained at 1123 K and higher temperatures, rutile as a single phase was detected. The TGA/DTA curves were dependent on the preparation of TiO_2 samples. The samples were also characterized by Fourier transform infrared spectroscopy and laser Raman spectroscopy.

On evaporation at room temperature of an aqueous mixture of Ln(SO4)3 (Ln=Ho, Yb, Lu) and (HOCH2CH2NH#)2SO4 in a molar ratio 1:16, crystal products were obtained. There were identified by means of x-ray powder diffraction and found to be isostructural. The results of elemental analysis and the mass losses by TG analysis indicated the formation of double sulfates. Their thermal decomposition in static air in temperature range from ambient up to 1173 K took place in a similar way, mainly in three steps which were not well defined. Oxysulfates were the final products of the termal decomposition.

Nanosized TiO2 plays an important role in new generation of solar cells. Dye-sensitized cells differ from conventional semiconductor devices in that they separate the function of light absorption from charge carrier transport. The device is based on a 10 micro-meters thick, optically transparent film of titanium dioxide grains, a few nanometers in size, coated with monolayer of charge-transfer dye to sensitize film for light harvesting. Comparative studies of nanocrystalline phases in TiO2 obtained by sol-gel method have been performed by X-ray diffraction (XRD), high resolution electron microscopy (HREM) and BET (Brunauer-Erett-Teller) adsorption of nitrogen gas at the temperature of liquid nitrogen for surface area determination. Using DTA/TGA analysis it was found that the temperature at anatase-rutile phase transition was 832 K. The grain diameter determined by XRD and HREM increased while BET surface area decrease with the increase of the calcinations temperature as well as during the phase transition from anatase to rutile.

Heksanuklearni klasteri [M_6X_(12)(ROH)_6]X_2 (M = Nb, Ta ; X = Cl, Br ; R = CH_3, C_2H_5) reagiraju s molekulama piridina (C_5H_5N) i daju nove klastere [M_6X_(12)(py)_6]X_2, u kojima su svi krajnji oktaedarski položaji zauzeti molekulama piridina. U etanolu spojevi [M_6X_(12)(ROH)_6]X_2 reagiraju s 4, 4'-dipiridilom (C_10H_8N_2) i daju [M_6X_(12)(4, 4'-dipy)_(6/2)]X_2, za koje se, prema spektroskopskim podacima, očekuje da šest molekula 4, 4'-dipiridila čine mostove između susjednih klasterskih jedinica tvoreći trodimenzijsku mrežu. Novi pripravljeni spojevi predstavljaju prve primjere heksanuklearnih halogenidnih klastera niobija i tantala u kojima su krajnji oktaedarski položaji zauzeti dušikovim atomima kao donorima.

Proces deamalgamacije u amalgamima slitina bogatih srebrom i kositrom istraživan je metalografijom, mjerenjem mikrotvrdoće, rentgenskom difrakcijom i diferencijalnom termičkom analizom. Dobiveni rezultati raspravljeni su s gledišta regeneracije otpadnog amalgama (reciklaže, tj. obnavljanja strukture i svojstava polaznih komponenti), kao i moguće uporabe ovog procesa u metalurgiji praha.

Oxygen donor complexes  1 of calcium hydrogenurate of the composition Ca(C_5H_3N_4O_3)_2L_3, L=(CH_3)_2SO, (CH_3)_2NCHO, if exposed to moist atmosphere, shortly washed with water or organic solvents containing small amount of water were transformed to hydrates Ca(C_5H_3N_4O_3)2 nH_2O, n=2, 3. The X-ray powder diffractograms as well as the thermogravimetric decomposition curves indicated distinct difference between dihydrate and trihydrate. Yet, thermally and structurally the trihydrate was more stable than dihydrate and the latter if exposed to moist atmosphere slowly transformed to trihydrate. If suspended in water the dihydrate and trihydrate recrystallize at room temperature to the most stable hydrate form of calcium hydrogenurate, the hexahydrate Ca(C5H3N4O3)2 6H2O. The solubility product constants for this hydrate were determined at different temperatures. Completely anhydrous, stable in inert atmosphere, nearly amorphous form of calcium hydrogenurate, Ca(C5H3N4O3)2 was obtained by the appropriate thermal treatment of Ca(C5H3N4O3)2L3 or Ca(C5H3N4O3)2 nH2O, n=2, 3, 6. Factors influecing formation of a particular hydrate form, structural, thermal and spectroscopic properties of all these calcium hydrogenurates are correlated. 1. N. Brničević, V. Babić-Ivančić, and H. Füredi-Milhofer, J. Inorg. Biochem., (1991) in press.

U vremenskom razdoblju od približno jedne godine otkrivene su četiri skupine visokotemperaturno-supravodljivih oksida. Prve dvije: La_(2-x)M_xCuO_4 (M = Ca, Sr, Ba) i L_nBa_2Cu_3O_(7-delta) (L_n = Y, elementi rijetkih zemalja) pokazuju prijelaz u supravodljivo stanje (T_c) kod ~40, odnosno ~90 K. Treću skupinu čine sustavi Bi-Ca-Sr-Cu-O i Tl-Ba-Ca-Cu-O s T_c ~100 K, koji ne sadrže elemente rijetkih zemalja, ali im je s prve dvije skupine zajednička prisutnost bakra. Konačno, četvrtoj skupini pripada K_(0, 4)B_(0, 6)BiO_3, koji ne sadrži ni elemente rijetkih zemalja ni bakar. Sve skupine posjeduju perovskitnu ili deformiranu perovskitnu strukturu. Razmatraju se uvjeti priprave, strukturna, mikrostrukturna, spektroskopska i transportna svojstva prvih triju skupina supravodljivih oksida.

Arrhenius plots of the thermal decomposition of Al2In12S21 in inert atmosphere of argon were done.

Three groups of high-temperature superconducting oxides: La_(2-x)Sr_xCuO_4, YBa_2Cu_3O_(7-delta) and Bi-Ca-Sr-Cu-O were prepared and their properties investigated. Solid state reaction of the starting components or coprecipitation methods were used in the preparation of superconducting samples. Thermal treatment of the components on the thermobalance gave insight into kinetic of alkaline-earth carbonates decomposition and the amount of oxygen present in the superconducting species. A method for the continuous control of the thermal reaction of the starting components is developed as well as the testing of high-quality superconducting samples. Two series of Bi-Ca-Sr-Cu-O systems were prepared, both with and without doping. The first one usually displays two Tc transitions, at 85 K and 110 K, while the second one, for suitable lead content and thermal treatment, as single high-Tc phase of 110 K was stabilized.

Detailed studies of the crystallization behaviour of the melt-spun Cu_50Ti_50 and Cu_66Ti_34 metallic glasses have been made by differential thermal analysis, X-ray diffraction and microhardness measurements. The samples were isochronally annealed from room temperature up to 1200 K. It was found that crystallization occurs at ~700 K for both glasses, and that for Cu_50Ti_50 this involves the appearance of tetragonal CuTi and Cu_4Ti_3 phases, while for Cu_66Ti_34 it involves the formation of the tetragonal Cu_3Ti_2 phase and orthorhombic Cu_2Ti and beta-Cu_3Ti phases. Crystallization products of both glasses showed strong preferred orientation, as evidenced by X-ray diffraction. The structural changes on annealing may be correlated with changes in the microhardness of the annealed samples.